Pain is the leading reason for adult outpatient and emergency department medical visits, impacting over 100 million Americans at a cost of over $600 billion dollars annually. Low back pain (LBP) represents 28% of this health-care problem and is the leading cause of disability, both in the United States and worldwide. Opioids are the most commonly prescribed drug class in the United States, and the majority of these prescriptions are for LBP. Despite the broad application of opioid therapy in LBP, the phenotypes of individuals who experience pain relief from opioid treatment have not been identified, leaving providers without clear guidance for safe and effective therapy. Given this staggering burden of disease and health-care utilization, clinical information regarding LBP widely populates the electronic health record (EHR), providing a valuable data source. However, this information presently has little meaning beyond the individual patient experience because the majority of pain-related data from the EHR is embedded in free text. Using EHR data may provide the crucial bridge to a better understanding of LBP. Thus, the central hypothesis of this proposal is that translating clinical experiences into discrete and analyzable data, specifically modeling opioid response phenotypes for patients with LBP, will identify clinically relevant phenotypic treatment responses. To test this hypothesis, this mentored career development project will adapt and apply natural language processing (NLP), data standardization, mining, and analysis tools to specifically model opioid response phenotypes for patients with LBP to characterize pain intensity, functional status, and pain interference with activity. Through integrated aims, this proposal will, 1) support the annotation of LBP and opioid note corpus, and the mapping of clinical concepts related to pain intensity, functional status, and pain interference with activities; 2) use NLP to identify and relate relevant opioid response phenotypes in patients with LBP in the EHR; and 3) characterize LBP phenotypes associated with opioid dose escalation. Clinical NLP uses statistical modeling to extract and transform high dimensional clinical data, which, when developed with the PI?s domain knowledge, creates a unique opportunity to understand LBP management, outcomes, and therapeutic efficacy. Ultimately this foundation may be used to predict clinical outcomes and responses to therapeutic interventions. Our long-term goal is to move beyond identifying disease phenotype profiles to create a system to identify treatment response phenotypes. Stratifying patients based on pain intensity, functional status, pain interference and other factors, we plan to identify potential cohorts that warrant further study from a genetic focus. This mentored career development grant (K08) will support a clinical expert?s adaptation of tools and training in a systematic method to allow growth toward a programmatic line of research that is incredibly responsive to the NIH pain research agenda and can transition to independent R01-level funding.